The cellular factors that determine the magnitude of the firing rate response of respiratory neurons to increased CO2 are typically attributed to acid-induced increased firing rate pathways. Although these activating pathways seem to explain the increased firing rate of chemosensitive neurons in many regions of the brainstem, a marked reduction in the firing rate response to hypercapnic acidosis (HA) has been observed in chemosensitive neurons from the locus coeruleus (LC) during postnatal development [1]. This limited response has been hypothesized to be due to the development of a decelerating pathway that arises from CO2/H+ activation of Ca2+ and Ca2+-activated K+ channels. Although this braking pathway may play an important role in setting the magnitude of the response to increased levels of CO2/H+ in LC neurons, limited attention has been paid to a braking pathway as a candidate mechanism exerting the observed limiting effect in central chemosensitivity [2]. In this work, a single-cell model was employed to simulate the chemosensitive behavior of LC neurons and investigate the effect of a putative limiting pathway driven by CO2 activated calcium currents and Ca+ activated K+ channels. The results from the model support the hypothesis that a calcium-activated braking pathway is responsible for the limited chemosensitivity of LC neurons.

[1] R. W. Putnam, J. A. Filosa, and N.A. Ritucci Am J Physiol Cell Physiol. 287:C1493-C1526 (2004).
[2] M Chernov, J. A. Daubenspeck, J. S. Denton, J. R. Pfeiffer, R. W. Putnam Am J Physiol Cell Physiol. 15:C278-C291 (2007).